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长期铁毒性诱导Sprague Dawley大鼠肾脏中抗氧化相关酶的基因表达及活性增强。

Stimulation of gene expression and activity of antioxidant related enzyme in Sprague Dawley rat kidney induced by long-term iron toxicity.

作者信息

Budak Harun, Kocpinar Enver Fehim, Gonul Nurdan, Ceylan Hamid, Erol Huseyin Serkan, Erdogan Orhan

机构信息

Atatürk University, Science Faculty, Department of Molecular Biology and Genetics, 25240 Erzurum, Turkey.

Atatürk University, Science Faculty, Department of Chemistry, 25240 Erzurum, Turkey.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2014 Nov;166:44-50. doi: 10.1016/j.cbpc.2014.07.002. Epub 2014 Jul 16.

DOI:10.1016/j.cbpc.2014.07.002
PMID:25038477
Abstract

The trace elements such as iron are vital for various enzyme activities and for other cellular proteins, but iron toxicity causes the production of reactive oxygen species (ROS) that causes alterations in morphology and function of the nephron. The present study was designed to determine the effect of long-term iron overload on the renal antioxidant system and to determine any possible correlation between enzymatic and molecular levels. Our data showed that reduced glutathione (GSH) levels, which is a marker for oxidative stress, strikingly decreased with a long-term iron overload in rat kidney. While renal mRNA levels of glucose 6-phosphate dehydrogenase (G6pd), 6-phosphogluconate dehydrogenase (6pgd) and glutathione peroxidase (Gpx) were significantly affected in the presence of ferric iron, no changes were seen for glutathione reductase (Gsr) and glutathione S-transferases (Gst). While the iron affected the enzymatic activity of G6PD, GSR, GST, and GPX, it had no significant effect on 6PGD activity in the rat kidney. In conclusion, we reported here that the gene expression of G6pd, 6pgd, Gsr, Gpx, and Gst did not correlate to enzyme activity, and the actual effect of long-term iron overload on renal antioxidant system is observed at protein level. Furthermore, the influence of iron on the renal antioxidant system is different from its effect on the hepatic antioxidant system.

摘要

铁等微量元素对于各种酶的活性以及其他细胞蛋白至关重要,但铁毒性会导致活性氧(ROS)的产生,进而引起肾单位形态和功能的改变。本研究旨在确定长期铁过载对肾脏抗氧化系统的影响,并确定酶水平和分子水平之间是否存在任何可能的相关性。我们的数据表明,作为氧化应激标志物的还原型谷胱甘肽(GSH)水平,在大鼠肾脏长期铁过载时显著降低。虽然在存在三价铁的情况下,肾组织中葡萄糖-6-磷酸脱氢酶(G6pd)、6-磷酸葡萄糖酸脱氢酶(6pgd)和谷胱甘肽过氧化物酶(Gpx)的mRNA水平受到显著影响,但谷胱甘肽还原酶(Gsr)和谷胱甘肽S-转移酶(Gst)未见变化。虽然铁影响了G6PD、GSR、GST和GPX的酶活性,但对大鼠肾脏中的6PGD活性没有显著影响。总之,我们在此报告,G6pd、6pgd、Gsr、Gpx和Gst的基因表达与酶活性不相关,长期铁过载对肾脏抗氧化系统的实际影响在蛋白质水平上得以观察到。此外,铁对肾脏抗氧化系统的影响与其对肝脏抗氧化系统的影响不同。

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